Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs

作者：Chiaro Joseph A; Baron Matthew D; del Alcazar Chelsea M; O' Donnell Patricia; Shore Eileen M; Elliott Dawn M; Ponder Katherine P; Haskins Mark E; Smith Lachlan J^*

来源：Bone, 2013, 55(1): 78-83.

DOI：10.1016/j.bone.2013.03.014

• Spine
• Trabecular bone
• Odontoid process
• Glycosaminoglycans
• Development
• Mucopolysaccharidosis

Introduction: Mucopolysaccharidosis I (MPS I) is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity leading to accumulation of poorly degraded dermatan and heparan sulfate glycosaminoglycans (GAGs). MPS I is associated with significant cervical spine disease, including vertebral dysplasia, odontoid hypoplasia, and accelerated disk degeneration, leading to spinal cord compression and kypho-scoliosis. The objective of this study was to establish the nature and rate of progression of cervical vertebral bone disease in MPS I using a canine model. %26lt;br%26gt;Methods: C2 vertebrae were obtained post-mortem from normal and MPS I dogs at 3, 6 and 12 months-of-age. Morphometric parameters and mineral density for the vertebral trabecular bone and odontoid process were determined using micro-computed tomography. Vertebrae were then processed for paraffin histology, and cartilage area in both the vertebral epiphyses and odontoid process were quantified. %26lt;br%26gt;Results: Vertebral bodies of MPS I dogs had lower trabecular bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD) than normals at all ages. For MPS I dogs, BV/TV, Tb.Th and BMD plateaued after 6 months-of-age. The odontoid process appeared morphologically abnormal for MPS I dogs at 6 and 12 months-of-age, although BV/TV and BMD were not significantly different from normals. MPS I dogs had significantly more cartilage in the vertebral epiphyses at both 3 and 6 months-of-age. At 12 months-of-age, epiphyseal growth plates in normal dogs were absent, but in MPS I dogs they persisted. %26lt;br%26gt;Conclusions: In this study we report reduced trabecular bone content and mineralization, and delayed cartilage to bone conversion in MPS I dogs from 3 months-of-age, which may increase vertebral fracture risk and contribute to progressive deformity. The abnormalities of the odontoid process we describe likely contribute to increased incidence of atlanto-axial subluxation observed clinically. Therapeutic strategies that enhance bone formation may decrease incidence of spine disease in MPS I patients.

• 出版日期2013-7